Effective pain management therapy often calls for an opioid analgesic. In addition to the desired analgesic effect, however, certain undesirable side effects, such as bowel dysfunction, nausea, constipation, among others, can accompany the use of an opioid analgesic. Such side effects may be due to opioid receptors being present outside of the central nervous system, principally in the gastrointestinal tract. Clinical and preclinical studies support the use of mPEG7-O-naloxol, a conjugate of the opioid antagonist naloxol and polyethylene glycol, to counteract undesirable side effects associated with use of opioid analgesics. When administered orally to a patient mPEG7-O-naloxol largely does not cross the blood brain barrier into the central nervous system, and has minimal impact on opioid-induced analgesia. See, e.g., WO 2005/058367; WO 2008/057579; Webster et al., “NKTR-118 Significantly Reverses Opioid-Induced Constipation,” Poster 39, 20th AAPM Annual Clinical Meeting (Phoenix, Ariz.), Oct. 10, 2009.
To move a drug candidate such as mPEG7-O-naloxol to a viable pharmaceutical product, it is important to understand whether the drug candidate has polymorphic forms, as well as the relative stability and interconversions of these forms under conditions likely to be encountered upon large-scale production, transportation, storage and pre-usage preparation. Solid forms of a drug substance are often desired for their convenience in formulating a drug product. No solid form of mPEG7-O-naloxol drug substance has been made available to date, which is currently manufactured and isolated as an oil in a free base form. Exactly how to accomplish this is often not obvious. For example the number of pharmaceutical products that are oxalate salts is limited. The free base form of mPEG7-O-naloxol has not been observed to form a crystalline phase even when cooled to −60° C. and has been observed to exist as a glass with a transition temperature of approximately −45° C. Furthermore, mPEG7-O-naloxol in its free base form can undergo oxidative degradation upon exposure to air. Care can be taken in handling the free base, for example, storing it under inert gas, to avoid its degradation. However, a solid form of mPEG7-O-naloxol, preferably one that is stable when kept exposed to air, is desired.